In isolated chromaffin cells, examination with Nomarski differential-interference microscopy reveals the presence of microspikes during vesicle release induced by Ba ions. This process is inhibited in the presence of concanavalin A. The mechanism of this effect is to be studied. If the exposure to acetylcholine is prolonged, the endplate membrane loses its sensitivity to acetylcholine. One explanation for this is Ca ions slowly crosses the membrane through the channels by acetylcholine, and that this Ca ions acts inside to close the channels. The time course of desensitization has been found to be slowed by reducing the Ca ions concentration in the bath. We propose to study the effects of alterations of the cellular Ca ions level on the time course of densensitization. Denervation of muscle increases the number of acetylcholine receptors in the membrane, and most, if not all, of these additional receptors are not in the endplate. These new receptors differ in some from those found at the endplate of innervated muscle. Alpha-Bungarotoxin blocks the endplate receptors of innervated muscle irreversibly. Studies with denervated muscles show the block to be partly reversible. However, the results of studies with labelled toxin suggest that the reversibility of the block is not due to loss of alpha-bungarotoxin. It seems that with time, the aplha-bungarotoxin-receptor complex changes in some way so as to become somewhat sensitive to acetylcholine. The properties of this receptor complex differ from those of the endplate receptor in innnervated muscle. Experiments are planned to examine differences between the two receptors and to learn more about the effects of innervation on the receptors.